Med-X, Journal Year: 2025, Volume and Issue: 3(1)
Published: Feb. 20, 2025
Language: Английский
Science, Journal Year: 2023, Volume and Issue: 380(6650)
Published: June 15, 2023
Aging is characterized by a decline in tissue function, but the underlying changes at cellular resolution across organism remain unclear. Here, we present Fly Cell Atlas, single-nucleus transcriptomic map of whole aging
Language: Английский
Citations
67
Cell Research, Journal Year: 2023, Volume and Issue: 33(6), P. 434 - 447
Published: April 13, 2023
Abstract Obesity imposes a global health threat and calls for safe effective therapeutic options. Here, we found that protein-rich diet significantly reduced body fat storage in fruit flies, which was largely attributed to dietary cysteine intake. Mechanistically, increased the production of neuropeptide FMRFamide (FMRFa). Enhanced FMRFa activity simultaneously promoted energy expenditure suppressed food intake through its cognate receptor (FMRFaR), both contributing loss effect. In body, signaling lipolysis by increasing PKA lipase activity. sweet-sensing gustatory neurons, appetitive perception hence We also demonstrated worked similar way mice via FF (NPFF) signaling, mammalian RFamide peptide. addition, or FMRFa/NPFF administration provided protective effect against metabolic stress flies without behavioral abnormalities. Therefore, our study reveals novel target development therapies obesity related diseases.
Language: Английский
Citations
28
Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)
Published: Feb. 21, 2023
Abstract Obesity caused by genetic and environmental factors can lead to compromised skeletal muscle function. Time-restricted feeding (TRF) has been shown prevent function decline from obesogenic challenges; however, its mechanism remains unclear. Here we demonstrate that TRF upregulates genes involved in glycine production ( Sardh CG5955 ) utilization Gnmt ), while Dgat2 , triglyceride synthesis is downregulated Drosophila models of diet- genetic-induced obesity. Muscle-specific knockdown dysfunction, ectopic lipid accumulation, loss TRF-mediated benefits, retains during aging reduces accumulation. Further analyses the purine cycle a diet-induced obesity model AMPK signaling-associated pathways model. Overall, our data suggest improves through modulations common distinct under different challenges provides potential targets for treatments.
Language: Английский
Citations
23
eLife, Journal Year: 2025, Volume and Issue: 13
Published: Jan. 29, 2025
Insulin plays a key role in metabolic homeostasis. Drosophila insulin-producing cells (IPCs) are functional analogues of mammalian pancreatic beta and release insulin directly into circulation. To investigate the vivo dynamics IPC activity, we quantified effects nutritional internal state changes on IPCs using electrophysiological recordings. We found that strongly modulates activity. activity decreased with increasing periods starvation. Refeeding flies glucose or fructose, two nutritive sugars, significantly increased whereas non-nutritive sugars had no effect. In contrast to feeding, perfusion did not affect This was reminiscent incretin effect, where ingestion drives higher than intravenous application. Contrary IPCs, Diuretic hormone 44-expressing neurons pars intercerebralis (DH44 PI Ns) responded perfusion. Functional connectivity experiments demonstrated these DH44 Ns do while other DH44Ns inhibit them. Hence, populations autonomously systemically sugar-sensing work parallel maintain Accordingly, activating small, satiety-like effect food-searching behavior reduced starvation-induced hyperactivity, hyperactivity. Taken together, demonstrate an integral part modulatory network orchestrates homeostasis adaptive response shifts state.
Language: Английский
Citations
1
Published: Feb. 10, 2025
Insulin plays a critical role in maintaining metabolic homeostasis. Since demands are highly dynamic, insulin release needs to be constantly adjusted. These adjustments mediated by different pathways, most prominently the blood glucose level, but also feedforward signals from motor circuits and neuromodulatory systems. Here, we analyze how inputs control activity of main source Drosophila – population Insulin-Producing Cells (IPCs) located brain. IPCs functionally analogous mammalian pancreatic beta cells, their location makes them accessible for vivo recordings intact animals. We characterized functional using single-nucleus RNA sequencing analysis, anatomical receptor expression mapping, connectomics, an optogenetics-based ‘intrinsic pharmacology’ approach. Our results show that IPC expresses variety receptors neuromodulators classical neurotransmitters. Interestingly, exhibit heterogeneous profiles, suggesting can modulated differentially. This is supported electrophysiological IPCs, which performed while activating populations modulatory neurons. analysis revealed some have effects on activity, such they inhibit one subset exciting another. Monitoring calcium across uncovered these responses occur simultaneously. Certain shifted towards excited state, others it inhibition. Taken together, provide comprehensive, multi-level neuromodulation insulinergic system .
Language: Английский
Citations
1
Nature Metabolism, Journal Year: 2025, Volume and Issue: unknown
Published: April 16, 2025
Abstract Cachexia, a severe wasting syndrome characterized by tumour-induced metabolic dysregulation, is leading cause of death in people with cancer, yet its underlying mechanisms remain poorly understood. Here we show that longitudinal full-body single-nuclei-resolution transcriptome analysis Drosophila model cancer cachexia captures interorgan dysregulations. Our study reveals the tumour-secreted interleukin-like cytokine Upd3 induces fat-body expression Pepck1 and Pdk , key regulators gluconeogenesis, disrupting glucose metabolism contributing to cachexia. Similarly, mouse models, observe IL-6–JAK–STAT-signalling-mediated induction Pck1 Pdk3 liver. Increased these genes fly, mouse, human correlates poor prognosis, hepatic emerges as previously unknown mechanism dysfunction This highlights conserved nature disruptions identifies potential therapeutic targets mitigate cancer.
Language: Английский
Citations
1
Seminars in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 138, P. 128 - 141
Published: April 16, 2022
Language: Английский
Citations
32
Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)
Published: March 23, 2024
Abstract Drosophila melanogaster is unique among animal models because it has a fully defined synthetic diet available to study nutrient-gene interactions. However, use of this limited adult studies due impaired larval development and survival. Here, we provide an adjusted formula that reduces the developmental period, restores fat levels, enhances body mass, rescues survivorship without compromise lifespan. To demonstrate application formula, explored pre-adult compositions therapeutic potential in model inherited metabolic disorder affecting metabolism branched-chain amino acids. We reveal rapid, specific, predictable nutrient effects on disease state consistent with observations from mouse patient studies. Together, our provides powerful means which examine interplay between across all life stages model.
Language: Английский
Citations
8
Published: Sept. 10, 2024
Insulin plays a critical role in maintaining metabolic homeostasis. Since demands are highly dynamic, insulin release needs to be constantly adjusted. These adjustments mediated by different pathways, most prominently the blood glucose level, but also feedforward signals from motor circuits and neuromodulatory systems. Here, we analyze how inputs control activity of main source Drosophila – population Insulin-Producing Cells (IPCs) located brain. IPCs functionally analogous mammalian pancreatic beta cells, their location makes them accessible for vivo recordings intact animals. We characterized functional using single-nucleus RNA sequencing analysis, anatomical receptor expression mapping, connectomics, an optogenetics-based ‘in-trinsic pharmacology’ approach. Our results show that IPC expresses variety receptors neuromodulators classical neurotransmitters. Interestingly, exhibit heterogeneous profiles, suggesting can modulated differentially. This is supported electrophysiological IPCs, which performed while activating populations modulatory neurons. analysis revealed some have effects on activity, such they inhibit one subset exciting another. Monitoring calcium across uncovered these responses occur simultaneously. Certain shifted towards excited state, others it inhibition. Taken together, provide comprehensive, multi-level neuromodulation insulinergic system .
Language: Английский
Citations
6
Environment International, Journal Year: 2024, Volume and Issue: 192, P. 109012 - 109012
Published: Sept. 17, 2024
Language: Английский
Citations
6